Genomic editors for localised population suppression

Abstract

Effective control of pest populations remains a major challenge for agriculture, public health, and conservation. While genetic control strategies such as the release of sterile males or individuals carrying dominant lethal alleles have achieved some success, they typically require repeated, large-scale releases due to immediate selection against costly alleles, limiting scalability and applicability to species that are difficult to rear in the laboratory. Recent CRISPR/Cas-based genome editing has enabled the development of more efficient genetic control methods that bias their own inheritance and impose a genetic load to achieve population suppression. These designs can potentially spread throughout an entire species range, making them unsuitable when only local or temporary suppression is needed. Here we explore self-limiting genetic strategies based on releasing males carrying autosomal genomic editors that create deleterious edits in essential genes. Unlike traditional approaches, where costly alleles are immediately purged, these editors can persist through multiple generations when creating female-specific or recessive edits, or when editing rates are less than 100%. This allows editors to survive in males, heterozygous carriers, or individuals unaffected by incomplete editing, trading immediate lethality for accumulated genetic load over time. Using deterministic population modelling, we demonstrate that homozygous releases of editors creating female-specific dominant or recessive edits require 45% and 50% fewer males than releasing individuals carrying dominant lethal alleles (RIDL), respectively, to achieve comparable suppression levels. Efficiency gains are further enhanced by targeting multiple genes simultaneously, with editors making female-specific recessive edits showing approximately 50% reduction in release requirements when targeting three genes compared to one - representing a 73% reduction compared to RIDL. Co-releasing editors with a second construct that temporarily boosts editor frequency can achieve efficiency comparable to previously proposed selectively neutral designs while maintaining temporal self-limitation. These results highlight promising alternative strategies for achieving localised, efficient, and self-limiting pest population control suitable for contexts requiring contained suppression.